Targeted delivery of NO donor and ROS scavenger for synergistic treatment of rheumatoid arthritis.
Biomed Pharmacother
; 174: 116540, 2024 May.
Article
em En
| MEDLINE
| ID: mdl-38579400
ABSTRACT
Rheumatoid arthritis (RA) is characterized by high level of reactive oxygen species (ROS) and proinflammatory cytokines, which facilitate the activation of the inflammatory signaling such as NF-κB pathway and exacerbate the development of inflammation. Herein, we designed a nanodrug by encapsulating the NO donor S-nitrosoglutathione (GSNO) into an emulsion and coating the surface with a polydopamine (PDA) layer to yield GSNO@PDA, which simultaneously scavenged the extra ROS and suppressed NF-κB signaling for potent RA treatment. To enhance the cellular uptake and NO generation efficiency, dextran sulfate (DS) and Cu2+ were anchored on the surface of GSNO@PDA to obtain the final formulation GSNO@PDA@DS. Our results demonstrated that GSNO@PDA@DS were successfully prepared and the modification of DS effectively boosted the cellular uptake of GSNO@PDA@DS. Moreover, GSNO@PDA@DS lowered cellular ROS and elevated intracellular NO, resulting in a decrease of M1 phenotype, inhibition of NF-κB pathway and down-regulation of proinflammatory cytokine tumor necrosis factor-α (TNF-α). Further in vivo studies confirmed that GSNO@PDA@DS significantly relieved symptoms and bone erosion by regulating the microenvironment of RA, highlighting the potential of GSNO@PDA@DS for RA therapy through ROS scavenging and NO-mediated suppression of inflammatory signaling.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Polímeros
/
Artrite Reumatoide
/
NF-kappa B
/
Espécies Reativas de Oxigênio
/
Doadores de Óxido Nítrico
/
S-Nitrosoglutationa
Limite:
Animals
Idioma:
En
Revista:
Biomed Pharmacother
/
Biomed. pharmacother
/
Biomedicine & pharmacotherapy
Ano de publicação:
2024
Tipo de documento:
Article